Is PARP14 p.Cys933Trp (c.2799C>G) pathogenic?

PARP14 p.Cys933Trp (c.2799C>G) is classified Uncertain significance in PARP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-10). AlphaMissense: likely pathogenic (0.9569); Absent from gnomAD v4.1.

How common is PARP14 p.Cys933Trp (c.2799C>G) in the general population?

PARP14 p.Cys933Trp (c.2799C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PARP14 p.Cys933Trp (c.2799C>G)?

AlphaMissense predicts likely pathogenic (score 0.9569) — an in-silico prediction, not a clinical call.

PARP14 p.Cys933Trp

c.2799C>G · rs142073365 · VCV2482838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9569 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9569	likely pathogenic · top 1% in PARP14
REVEL	0.406	indeterminate
SaProt	LLR -17.11	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.048	GERP -4.2, phastCons 0.97
Regional constraint	o/e 0.83	unconstrained · MANE · 47 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	19.09	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PARP14
Protein: p.Cys933Trp
Coding: c.2799C>G
MANE Select: NM_017554
dbSNP: rs142073365
Type: single nucleotide variant
Location: chr3:122701353 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.00 · 47 PDB
Residue 933: the macro 1 domain; an α-helix

Full PARP14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PARP14 p.Pro1200Leu Uncertain significance ★★ ⚠ same type
PARP14 p.Ala1513Val Benign ★★ same type
PARP14 p.Ala864= Benign ★★ same type
PARP14 p.Asp488Asn Benign ★★ same type
PARP14 p.Gln1413Pro Benign ★★ same type
PARP14 p.Ala1187Ser Uncertain significance ★ ⚠ same type
PARP14 p.Ala1202Ser Uncertain significance ★ ⚠ same type
PARP14 p.Ala1350Asp Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/parp14-p-cys933trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown